Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

• Published in: PloS one Vol. 10; no. 5; p. e0128372
• Main Authors: Prabu, Paramasivam, Rome, Sophie, Sathishkumar, Chandrakumar, Aravind, Sankaramoorthy, Mahalingam, Balakumar, Shanthirani, Coimbatore Subramanian, Gastebois, Caroline, Villard, Audrey, Mohan, Viswanathan, Balasubramanyam, Muthuswamy
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.05.2015; Public Library of Science (PLoS)
• Subjects: Adult; Animals; Asian people; Asians; Biomarkers; Biomarkers - blood; Blood Glucose - metabolism; Brain research; Cardiovascular diseases; Care and treatment; Case-Control Studies; Cholesterol; Cholesterol - blood; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Disease prevention; Education; Ethnic factors; Ethnic Groups; Etiology; Fasting; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Glucose; Glucose Intolerance; Glucose tolerance; Glucose Tolerance Test; Glycated Hemoglobin A - metabolism; Hemoglobin; Homeostasis; Humans; Insulin; Insulin - blood; Insulin Resistance; Laboratories; Life Sciences; Male; Metabolism; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; Minority & ethnic groups; miRNA; Obesity; Patients; Phenotype; Population studies; Prediabetic state; Prediabetic State - blood; Prediabetic State - ethnology; Prediabetic State - genetics; Prediabetic State - pathology; Risk factors; Studies; Type 2 diabetes; India; Humans; Middle Aged; Insulin/blood; Male; Glucose Intolerance; Case-Control Studies; Prediabetic State/blood/ethnology/genetics/pathology; Ethnic Groups; Glycosylated/metabolism; Cholesterol/blood; Experimental/blood/genetics/pathology; Type 2/blood/ethnology/genetics/pathology; Female; Biomarkers/blood; Adult; Hemoglobin A; MicroRNAs/blood/genetics; Glucose Tolerance Test; Fasting; Blood Glucose/metabolism; Insulin Resistance; Gene Expression Regulation; Diabetes Mellitus; Inbred C57BL; Phenotype; Animals; Mice
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128372

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.